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Chromium contributes to human bronchial epithelial cell carcinogenesis by activating Gli2 and inhibiting autophagy.
- Source :
- Toxicology Research; May2017, Vol. 6 Issue 3, p324-332, 9p
- Publication Year :
- 2017
-
Abstract
- Occupational and environmental inhalation exposure to hexavalent chromium [Cr(VI)] compounds has been confirmed to cause respiratory system injury and cancer. The molecular mechanisms of chromium carcinogenesis still require further study. We established Cr(VI)-transformed cells (BEAS-2B-Cr) after chronic exposure of immortalized normal human bronchial epithelial BEAS-2B cells to low doses of Cr(VI), which obtained the ability of anchorage-independent growth. BEAS-2B-Cr cells not only exhibited stronger proliferation, migration, invasion and tumorigenesis capabilities but also acquired an altered and distinct Gli2 gene expression pattern compared with untreated parental BEAS-2B cells (P-NC) and the control BEAS-2B cells (NC). Interestingly, we found that activation of Gli2 by Cr(VI) treatment prevented the induction of autophagy. Using a gene silencing approach, we showed that Gli2 plays an important role in the malignant properties of BEAS-2B-Cr cells. Downregulation of Gli2 induced autophagy and inhibited cell proliferation and colony forming abilities, which are both upregulated in BEAS-2B-Cr cells compared to NC cells. In addition, inhibition of autophagy by 3-methyladenine (3-MA) partially suppressed the cytotoxicity induced by GANT61-induced inhibition of Gli2. These results demonstrate that hexavalent chromium Cr(VI) activates Gli2 to promote the proliferation of BEAS-2B-Cr cells by inhibition of autophagy, which contributes to human bronchial epithelial cell carcinogenesis. Gli2 may not only play an important role in lung cancer pathogenesis, but also be a promising early indicator in monitoring exposure to chromium. [ABSTRACT FROM AUTHOR]
- Subjects :
- HEXAVALENT chromium
CHROMIUM compounds
AUTOPHAGY
EPITHELIAL cells
CARCINOGENESIS
Subjects
Details
- Language :
- English
- ISSN :
- 2045452X
- Volume :
- 6
- Issue :
- 3
- Database :
- Complementary Index
- Journal :
- Toxicology Research
- Publication Type :
- Academic Journal
- Accession number :
- 143249550
- Full Text :
- https://doi.org/10.1039/c6tx00372a